Early Growth Response (Egr) genes may have an important role in mammalian sympathetic nervous system development. Egr mediated gene transcription is essential for differentiation of sympathetic nervous system derived PC12 and neuroblastoma cell lines. However, their role in sympathetic neuron development has never been addressed in vivo. We have outlined a training and research program that will: 1) Characterize the sympathetic nervous system defects in Egr3-deficient mice; 2) determine which Egr gene family members are expressed in sympathetic neurons in vivo; and 3) explore the role of signal transduction pathways involving neurotrophin-3 (NT-3) and upstream transcriptional regulators such as CREB in regulating Egr gene expression during sympathetic neuron development. A greater understanding of the signal transduction mechanisms related to growth factor mediated differentiation and survival may provide important insights into the pathogenesis of tumors and neurodegenerative diseases involving sympathetic neurons. [unreadable] [unreadable]